A Cyclic-di-GMP signalling network regulates biofilm formation and surface associated motility of Acinetobacter baumannii 17978
A Cyclic-di-GMP signalling network regulates biofilm formation and surface associated motility of Acinetobacter baumannii 17978
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DOI：
10.1038/s41598-020-58522-5
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发表时间：
2020-02-06
影响因子：
4.6
通讯作者：
Uhlin, Bernt Eric
中科院分区：
文献类型：
--
作者：
Ahmad, Irfan;Nygren, Evelina;Uhlin, Bernt Eric
鲍曼不动杆菌已成为医院中日益严重的多重耐药威胁，也是全世界常见的机会性医院病原体。然而，这种细菌的发病机制和生理学的分子细节在很大程度上仍有待阐明。在这里，我们识别和表征 c-di-GMP 信号网络，并评估其在生物膜形成和表面相关运动中的作用。生物信息分析揭示了鲍曼不动杆菌菌株 17978 基因组中的 11 个 c-di-GMP 代谢蛋白（GGDEF/EAL 结构域蛋白）的候选基因。通过分子克隆和在模式生物鼠伤寒沙门氏菌和霍乱弧菌中的表达来评估所编码蛋白的酶活性。 11 个 GGDEF/EAL 蛋白中有 10 个改变了鼠伤寒沙门氏菌的 rdar 形态型和霍乱弧菌的皱纹形态型。三种 GGDEF 蛋白的过度表达对刚果红琼脂平板上鲍曼不动杆菌集落形成产生显着影响。发现不同的 GGDEF/EAL 蛋白组在过度表达后会改变鲍曼不动杆菌的生物膜形成和表面相关运动。 GGDEF 蛋白 A1S_3296 是调节大集落形成、生物膜形成和表面相关运动的主要二鸟苷酸环化酶。 AIS_3296 促进 Csu 菌毛介导的生物膜形成。我们得出的结论是，鲍曼不动杆菌中的功能性 c-di-GMP 信号网络调节这种日益重要的机会性细菌病原体的生物膜形成和表面相关运动。
Acinetobacter baumannii has emerged as an increasing multidrug-resistant threat in hospitals and a common opportunistic nosocomial pathogen worldwide. However, molecular details of the pathogenesis and physiology of this bacterium largely remain to be elucidated. Here we identify and characterize the c-di-GMP signalling network and assess its role in biofilm formation and surface associated motility. Bioinformatic analysis revealed eleven candidate genes for c-di-GMP metabolizing proteins (GGDEF/EAL domain proteins) in the genome of A. baumannii strain 17978. Enzymatic activity of the encoded proteins was assessed by molecular cloning and expression in the model organisms Salmonella typhimurium and Vibrio cholerae. Ten of the eleven GGDEF/EAL proteins altered the rdar morphotype of S. typhimurium and the rugose morphotype of V. cholerae. The over expression of three GGDEF proteins exerted a pronounced effect on colony formation of A. baumannii on Congo Red agar plates. Distinct panels of GGDEF/EAL proteins were found to alter biofilm formation and surface associated motility of A. baumannii upon over expression. The GGDEF protein A1S_3296 appeared as a major diguanylate cyclase regulating macro-colony formation, biofilm formation and the surface associated motility. AIS_3296 promotes Csu pili mediated biofilm formation. We conclude that a functional c-di-GMP signalling network in A. baumannii regulates biofilm formation and surface associated motility of this increasingly important opportunistic bacterial pathogen.